Psychoactive cannabinoid compounds exert their effects in the brain through the CB1 receptor, a member of the G protein-coupled receptor superfamily. In both the rat and human, the CB1 receptor is highly expressed throughout the basal ganglia, including the striatum, and this receptor is thought to mediate the distinct actions of delta9-THC and other cannabinoids in these nuclei. Moreover, endogenous CB1 ligands, such as the arachidonate derivative anandamide, are present in the striatum and represent a cannabimimetic signalling system about which little is known. The aim of this proposal is to investigate functional consequences of CB1 receptor activation in the rat striatum, using electrophysiological measurements in brain slices and in an established corticostriatal co-culture system. It is proposed that CB1 receptor activation leads to inhibition of glutamate release from corticostriatal afferent neurons. Whole cell EPSCs and extracellular field potentials will be measured in the presence of a CB1 agonist and compared to a control baseline in the absence of drug. A second set of studies will attempt to evoke striatal LTD in the presence or absence of a CB1 antagonist in order to test the involvement of CB1 receptors in the phenomenon of striatal LTD.